Anticonvulsant effects of mu (DAGO) and delta (DPDPE) enkephalins in rats

Abstract

The effects of highly selective mu and delta opioid peptide agonists were determined in two rat models of experimentally-induced convulsions, the flurothyl threshold test and the maximal electroshock test. Intracerebroventricular injections of the mu selective enkephalin DAGO (0.3-2.2 nmol) resulted in a dose-related protection in both seizure models. Pretreatment with a low dose of naloxone (29 nmol) or the irreversible mu antagonist [beta]-FNA (21 nmol), but not the delta opioid antagonist ICI 154,129 (50 nmol), antagonized the anticonvulsant actions of DAGO. Intracerebroventricular injections of the delta selective enkephalin DPDPE (70-140 nmol) also resulted in seizure protection. These effects were selectively antagonized by the delta antagonist ICI 174,864 (2.8 nmol), but not by pretreatment with [beta]-FNA. Thus, using agonists and antagonists highly selective for mu and delta opioid receptors, anticonvulsant actions of enkephalin have been described against chemically- and electrically-induced convulsions in rats.